Cardiovascular System - Blood Vessel Development
Blood develops initially within the core of "blood islands" in the mesoderm. During development, there follows a series of "relocations" of the stem cells to different organs within the embryo. In the adult, these stem cells are located in the bone marrow. At the time when blood first forms, there are no bones!
Angioblasts initially form small cell clusters (blood islands) within the embryonic and extraembryonic mesoderm. These blood islands extend and fuse together making a primordial vascular network. Within these islands the peripheral cells form endothelial cells while the core cells form blood cells (haemocytoblasts).
Recent work has shown that the formation of the initial endothelial tube is by a process of coalescence of cellular vacuoles within the developing endothelial cells, which fuse together without cytoplasmic mixing to form the blood vessel lumen.
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Some Recent Findings
|More recent papers|
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Dan Kai, Qiang-Li Wang, Hai-Jie Wang, Molamma P Prabhakaran, Yanzhong Zhang, Yu-Zhen Tan, Seeram Ramakrishna Stem cell loaded nanofibrous patch promotes the regeneration of infarcted myocardium with functional improvement in rat model. Acta Biomater: 2014; PMID:24576580 Carlos Sabu Alvez, Luis Otavio Carvalho de Moraes, Sergio R Marques, Roberto C Tedesco, Leandro J C Harb, Jose F Rodríguez-Vázquez, Jose R Mérida-Velasco, Luis Garcia Alonso Analysis by Light, Scanning, and Transmission Microscopy of the Intima Synovial of the Temporomandibular Joint of Human Fetuses during the Development. Anat Res Int: 2014, 2014();732720 PMID:24527214 N S Opanasenko, V I Klimenko, A É Kshanovskiĭ, A V Tereshkovich, M I Kalenichenko, B N Konik, R S Demus, O K Obremskaia, L I Levanda, V A Kononenko, I Iu Mikitenko [Diagnosis and surgical treatment of cystic pulmonary hypoplasia with aortic blood supply]. Klin Khir: 2013, (12);44-8 PMID:24502010 M S Opanasenko, V I Klymenko, R S Demus, B M Konik, O V Tereshkovych, M I Kalenychenko, V B Bychkovs'kyĭ, O K Obrems'ka, L I Levanda, V A Kononenko, O E Kshanovs'kyĭ, I Iu Mykytenko [Pulmonary arteriovenous fistulas]. Klin Khir: 2013, (11);41-6 PMID:24501988 Abolhassan Shakeri, Masoud Pourisa, Abdolreza Deldar, Mohamad Goldust Anatomic variations of aortic arch branches and relationship with diameter of aortic arch by 64-row CT angiography. Pak. J. Biol. Sci.: 2013, 16(10);496-500 PMID:24498817
Recent work has shown that the formation of the initial endothelial tube is by a process of coalescence of cellular vacuoles within the developing endothelial cells, which fuse together without cytoplasmic mixing to form the blood vessel lumen. 
Endothelial Tube Formation
The following data is from a recent review.
|Shh||Loss of Shh results in lack of arterial identity in zebrafish. Shh acts upstream of VEGF.|
|VEGF||VEGF acts downstream of Shh signaling to activate Notch via the PLCγ/ERK pathway in zebrafish. Mutant mice expressing only VEGF188 lack arterial differentiation.|
|Nrp1||Null mice display impaired arterial differentiation. Nrp1 is involved in a positive feedback loop of VEGF signaling.|
|Notch||Notch acts downstream of Shh and VEGF signaling in zebrafish. Notch1; Notch4 mutant mice have abnormal vascular development.|
|Dll4||Null mice lack arterial specification.|
|Dll1||Null mice fail to maintain arterial identity.|
|Hey1/2 (Grl)||Null mice lack arterial specification. Lack of grl in zebrafish results in loss of arterial specification.|
|Foxc1/c2||Foxc1; Foxc2 mutant mice lack arterial specification. Foxc1 and Foxc2 directly regulate Dll4 and Hey2 expression. Foxc1 and Foxc2 are also involved in lymphatic vessel development.|
|Sox7/18||Lack of Sox7/18 results in loss of arterial identity in zebrafish.|
|Snrk-1||Snrk-1 acts downstream or parallel to Notch signaling in zebrafish.|
|Dep1||Dep1 acts upstream of PI3K in arterial specification in zebrafish.|
|Crlr||Shh regulates VEGF activity by controlling crlr expression in zebrafish.|
|EphrinB2||Null mice lack boundaries between arteries and veins. EphrinB2 is involved in lymphatic vascular remodeling and maturation.|
|COUP-TFII||COUP-TFII suppresses arterial cell fate by inhibiting Nrp1 and Notch. COUP-TFII also interacts with Prox1 to regulate lymphatic gene expression.|
|EphB4||Null mice lack boundaries between arteries and veins.|
|Sox18||Null mice fail to specify lymphatic endothelial cells. Sox18 induces Prox1 expression.|
|Prox1||Prox1 induces lymphatic markers and maintains lymphatic cell identity.|
Vascular Endothelial Growth Factor
Growing blood vessels follow a gradient generated by tagret tissues/regions of Vascular Endothelial Growth Factor (VEGF) to establish a vascular bed. Recent findings suggest that Notch signaling acts as an inhibitor for this system, preventing sprouting of blood vessels.
Notch is a transmembrane receptor protein involved in regulating cell differentiation in many developing systems.
Regulators of Growth
The following data is from a review article on ovary vascular development.
Stimulators of Angiogenisis
Inhibitors of Angiogenisis
Vein Light Microscopy
The entire developing and adult cardiovascular system (blood vessels and heart) is lined by a simple squamous epithelium. (Stain - Haematoxylin Eosin)
Capillary Electron Microscopy
| Blood Capillary Electron Micrograph
A blood capillary lumen (lu) lined by an endothelial cell (en) is surrounded by a continuous basal lamina (arrowhead) in which is incorporated a pericyte (p).
Extracellular matrix collagen bundles at top of image.
Scale bar 1 μm
| Blood Capillary Electron Micrograph
Scale bar 1 μm
Cardiac Blood Vessels
Earliest vessels in the heart wall develop subepicardially (beneath the outside surface of the heart) near the apex at Carnegie stage 15, which then extends centripetally and at stage 17 coronary arterial stems communicate with the aortic lumen.
(Text modified from: )
- ↑ 1.0 1.1 Tsutomu Kume Specification of arterial, venous, and lymphatic endothelial cells during embryonic development. Histol. Histopathol.: 2010, 25(5);637-46 PMID:20238301 | PMC2899674
- ↑ Per Wasteson, Bengt R Johansson, Tomi Jukkola, Silke Breuer, Levent M Akyürek, Juha Partanen, Per Lindahl Developmental origin of smooth muscle cells in the descending aorta in mice. Development: 2008, 135(10);1823-32 PMID:18417617
- ↑ Frances A High, Min Min Lu, Warren S Pear, Kathleen M Loomes, Klaus H Kaestner, Jonathan A Epstein Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development. Proc. Natl. Acad. Sci. U.S.A.: 2008, 105(6);1955-9 PMID:18245384
- ↑ Morayma Reyes, Arkadiusz Dudek, Balkrishna Jahagirdar, Lisa Koodie, Paul H Marker, Catherine M Verfaillie Origin of endothelial progenitors in human postnatal bone marrow. J. Clin. Invest.: 2002, 109(3);337-46 PMID:11827993
- ↑ H G Augustin Vascular morphogenesis in the ovary. Baillieres Best Pract Res Clin Obstet Gynaecol: 2000, 14(6);867-82 PMID:11141338
- ↑ Benoit Detry, Françoise Bruyère, Charlotte Erpicum, Jenny Paupert, Françoise Lamaye, Catherine Maillard, Bénédicte Lenoir, Jean-Michel Foidart, Marc Thiry, Agnès Noël Digging deeper into lymphatic vessel formation in vitro and in vivo. BMC Cell Biol.: 2011, 12();29 PMID:21702933 | PMC3141733 | BMC Cell Biol.
- ↑ K Turner, V Navaratnam The positions of coronary arterial ostia. Clin Anat: 1996, 9(6);376-80 PMID:8915616
A J Davidson, L I Zon Turning mesoderm into blood: the formation of hematopoietic stem cells during embryogenesis. Curr. Top. Dev. Biol.: 2000, 50();45-60 PMID:10948449
Kathleen E McGrath, Anne D Koniski, Jeffrey Malik, James Palis Circulation is established in a stepwise pattern in the mammalian embryo. Blood: 2003, 101(5);1669-76 PMID:12406884
Click on the listed keywords below (used to search the external database) the most current references on Medline will be displayed.
- angioblasts stem cells in blood islands generating endothelial cells
- angiogenesis the formation of blood vessels also called vasculogenesis in the embryo
- blood islands earliest sites of blood vessel and blood cell formation, seen mainly on yolk sac chorion
- vascular endothelial growth factor (VEGF) protein growth factor family that stimulates blood vessel growth, a similar factor can be found in the placenta (PIGF).
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Cite this page: Hill, M.A. (2014) Embryology Cardiovascular System - Blood Vessel Development. Retrieved March 7, 2014, from http://embryology.med.unsw.edu.au/embryology/index.php?title=Cardiovascular_System_-_Blood_Vessel_Development
- Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G